The overall objective of this research is an increased understanding of the physiological and biochemical basis of drug action on bulbo-spinal motor pathways. The immediate objectives include exploration of motor pathways in which 5-hydroxytryptamine and gamma- aminobutyric acid are likely involved as synaptic transmitters (e.g., bulbo-spinal inhibition and facilitation and presynaptic inhibition). Using pharmacological agents which alter synthesis, storage, release or receptor combination of these putative transmitters, the effects of altered metabolism or receptor blockade of the transmitter under investigation will be correlated with changes in spinal reflex activity. Electrophysiological dissections will be carried out to localize the physiological site of drug action. This will be done by measurements of neuronal excitability, afferent terminal depolarization, evoked reflexes and the effects of microiontophoretic application of agents to single neurons. Particular attention will be focused on the role of 5- hydroxytryptamine and gamma-aminobutyric acid in modulating afferent terminal depolarization. The results of this kind of study will help place the pharmacological control of motor pathways within the central nervous system on a firmer physiological and biochemical basis. In the process of reaching this goal important evidence should be produced for and against the transmitter role of 5-hydroxytryptamine and gamma- aminobutyric acid.